Design and Synthesis of a Fluorescent Probe for Zn2+, 5,7-Bis(N,N-dimethylaminosulfonyl)-8-hydroxyquinoline-Pendant 1,4,7,10-Tetraazacyclododecane and Zn2+-Dependent Hydrolytic and Zn2+-Independent Photochemical Reactivation of Its Benzenesulfonyl-Caged Derivative

• Published in: Inorganic chemistry Vol. 49; no. 3; pp. 888 - 899
• Main Authors: Ohshima, Ryosuke, Kitamura, Masanori, Morita, Akinori, Shiro, Motoo, Yamada, Yasuyuki, Ikekita, Masahiko, Kimura, Eiichi, Aoki, Shin
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.02.2010
• Subjects: Fluorescent Dyes - chemical synthesis; Fluorescent Dyes - chemistry; Hydrolysis; Ligands; Molecular Structure; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Photochemistry; Sulfones - chemistry; Zinc - chemistry
• ISSN: 0020-1669; 1520-510X
• DOI: 10.1021/ic901279t

We previously reported on a 8-quinolinol-pendant cyclen (L5) as a Zn2+ fluorophore (cyclen = 1,4,7,10-tetraazacyclododecane) and its caged derivative, 8-(benzenesulfonyloxy)-5-(N,N-dimethylaminosulfonyl)quinolin-2-ylmethyl-pendant cyclen (BS-caged-L5), which can be reactivated by hydrolysis of benzenesulfonyl group upon complexation with Zn2+ at neutral pH to give a 1:1 Zn2+−L5 complex (Zn(H−1L5)). We report herein on the synthesis of 5,7-bis(N,N-dimethylaminosulfonyl)-8-hydroxyquinolin-2-ylmethyl-pendant cyclen (L6) and its caged derivative (BS-caged-L6) for more sensitive and more efficient cell-membrane permeability than those of L5 and BS-caged-L5. By potentiometric pH, 1H NMR, and UV−vis spectroscopic titrations, the deprotonation constants pK a1−pK a6 of H5L6 were determined to be <2, <2, <2, 2.5 ± 0.1 (for the 8-OH group of the quinoline moiety), 9.7 ± 0.1, and 10.8 ± 0.1 at 25 °C with I = 0.1 (NaNO3). The results of 1H NMR, potentiometric pH, UV−vis, and fluorescent titrations showed that L6 rapidly forms a 1:1 complex with Zn2+ (Zn(H−1L6)), the dissociation constant of which is 50 fM at pH 7.4. The fluorescent emission of Zn(H−1L6) at 478 nm is 32 times as large as that of L6 (excitation at 370 nm), and the fluorescent quantum yield of Zn(H−1L6) (ΦF = 0.41) is much greater than that of Zn(H−1L5) (ΦF = 0.044). The BS-caged-L6 was reactivated by hydrolysis of the benzenesulfonyl moiety more rapidly (completes in 30 min at pH 7.4 at 37 °C) than BS-caged-L5, presumably enabling the practical detection of Zn2+ in sample solutions and living cells. The photochemical deprotection of BS-caged-L6 and the cell membrane permeability of L6 and BS-caged-L6 are also described.